The Effect of Vitamin D Supplementation on Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Gan J, Galer P, Ma D, Chen C, Xiong T (2019) J Child Adol Psychop 29(9) 670-687. DOI: 10.1089/cap.2019.0059, Epub 2019 Aug 1.

Web URL: Read this and related abstracts on PubMed here

Abstract:

Objective:

A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the benefits and harms of vitamin D supplementation for attention-deficit/hyperactivity disorder (ADHD) patients.

Methods:

We followed the standard methodological procedures of the Cochrane Handbook for Systematic Reviews of Intervention. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Science and Conference Proceedings Citation Index-Social Science and Humanities (Web of Science), ClincalTrials.gov, and World Health Organization's International Clinical Trials Registry Platform were searched for RCTs in January 2019. Independently, two authors (J.G., T.X.) extracted data, assessed the risk of bias, combined the data, and graded evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Our primary outcomes were assessed through rating scales of ADHD severity. Secondary outcomes measured were the possible adverse effects of vitamin D supplementation and vitamin D status after supplementation for ADHD.

Results:

We included four RCTs with 256 children addressing vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms.

Vitamin D supplementation demonstrated a small but statistically significant improvement in ADHD total scores, inattention scores, hyperactivity scores, and behavior scores. The improvement was likely limited due to the low to very low quality of evidence in the literature. There was no statistically significant improvement in oppositional scores.

Reported adverse events in the vitamin D group were mild and not significantly different from the control group. Vitamin D supplementation increased serum vitamin D levels and the ratio of patients with sufficient vitamin D levels.

Conclusions:

Vitamin D supplementation as adjunctive therapy to methylphenidate appeared to reduce ADHD symptoms without serious adverse events, associated with improved vitamin D status.

However, considering the generally low strength of evidence, well-designed RCTs are needed to determine the efficacy and safety of vitamin D supplementation for both children and adults with ADHD, especially in the setting of a combination of vitamin D and other ADHD treatments.

FAB RESEARCH COMMENT:

A lack of Vitamin D in mothers during pregnancy has repeatedly been linked with higher risks for ADHD and other neurodevelopmental disorders, as well as with poorer cognitive development in general.

Consistent with this, animal studies have provided clear evidence that Vitamin D deficiency during brain development leads to permanent brain changes in the offspring, which raise their lifelong risk for disorders of attention, motor control and perception.

Children with ADHD (and autism) have also been reported to show lower blood levels of Vitamin D than matched controls.

But what has not been clear is whether supplementation with Vitamin D at this stage of life might help to reduce ADHD symptoms.

Results from this systematic review and meta-analysis of randomised controlled treatment trials provides preliminary evidence that it might, as significant symptom improvements were found for ADHD children receiving Vitamin D compared with placebo supplements.

As expected, supplementation increased the chldren's blood levels of Vitamin D, and no adverse effects were observed.

This finding came from only four small trials, so further, large-scale trials are now clearly warranted.

It's also important to emphasise that 'ADHD' is not a unitary condition, but an 'umbrella label' that conceals considerable variability. The diagnosis is purely descriptive, and ADHD shows strong overlaps with many other developmental and mental as well as physical health conditions, as well as with normal individual variations in behaviour and cognition.

Meanwhile, however, given that deficiency or insufficiency of Vitamin D is very common, and linked with other mental and physical heath problems as well as impaired immunity, there is already a very good case for ensuring that all children (and adults) have an adequate intake of Vitamin D.

See the associated news article and FAB comment here: